rs147908313
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001122681.2(SH3BP2):c.932G>A(p.Gly311Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
SH3BP2
NM_001122681.2 missense
NM_001122681.2 missense
Scores
1
3
14
Clinical Significance
Conservation
PhyloP100: 0.641
Genes affected
SH3BP2 (HGNC:10825): (SH3 domain binding protein 2) The protein encoded by this gene has an N-terminal pleckstrin homology (PH) domain, an SH3-binding proline-rich region, and a C-terminal SH2 domain. The protein binds to the SH3 domains of several proteins including the ABL1 and SYK protein tyrosine kinases , and functions as a cytoplasmic adaptor protein to positively regulate transcriptional activity in T, natural killer (NK), and basophilic cells. Mutations in this gene result in cherubism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAdExome4 at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SH3BP2 | NM_001122681.2 | c.932G>A | p.Gly311Asp | missense_variant | 8/13 | ENST00000503393.8 | |
SH3BP2 | NM_001145856.2 | c.1103G>A | p.Gly368Asp | missense_variant | 8/13 | ||
SH3BP2 | NM_001145855.2 | c.1016G>A | p.Gly339Asp | missense_variant | 8/13 | ||
SH3BP2 | NM_003023.4 | c.932G>A | p.Gly311Asp | missense_variant | 8/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH3BP2 | ENST00000503393.8 | c.932G>A | p.Gly311Asp | missense_variant | 8/13 | 1 | NM_001122681.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152136Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251052Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135824
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GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461298Hom.: 0 Cov.: 36 AF XY: 0.0000110 AC XY: 8AN XY: 726970
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152136Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74308
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Fibrous dysplasia of jaw Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 311 of the SH3BP2 protein (p.Gly311Asp). This variant is present in population databases (rs147908313, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with SH3BP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 571079). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SH3BP2 protein function with a negative predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;T;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.;L;L;.;L
MutationTaster
Benign
N;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Uncertain
Sift
Benign
D;D;D;D;D;D
Sift4G
Benign
T;T;T;T;T;T
Polyphen
B;.;B;B;.;B
Vest4
MVP
MPC
0.39
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 25
Find out detailed SpliceAI scores and Pangolin per-transcript scores at